Frizzled induced Van Gogh phosphorylation regulates PCP signaling. Lindsay Kelly, Marek Mlodzik. Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY.

   A great deal of work has focused on how individual cells within an epithelium adopt a defined polarity. However, the process by which polarity is coordinated between cells is poorly understood. Competing hypotheses propose that cells polarize in response to a long-range diffusible signal or through a cell-cell relay mechanism. Because the core planar cell polarity (PCP) protein complexes that signal across cell membranes are asymmetric, it is difficult to assess which interaction is more important for the transduction of polarity information or the instructive long-range signal(s). It has previously shown that the core PCP protein, Van Gogh (Vang) functions as a Frizzled (Fz) receptor in signal receiving cells to sense Fz activity levels. Our preliminary data suggest that a novel pathway exists downstream of Vang that functions to interpret and relay polarity information to neighboring cells. We have also observed that Vang is phosphorylated in response to Fz signaling and identified that a single residue substitution of Vang Y341F generates a phosphorylation defective mutant. In vivo, this mutant fails to localize normally and does not rescue Vang function in PCP. We are using a combination of of genetic and biochemical approaches to determine the kinase(s) that phosphorylate Vang Tyr341. Identification of this kinase will provide an important entry point into the presumed downstream signaling cascade.